FDA Guidance Focuses on Considering Uncertainty in Benefit-Risk Determinations

Posted September 4, 2019

The Food and Drug Administration (FDA) has issued final guidance describing the rigorous methods it uses when considering uncertainty during benefit-risk determinations related to premarket decisions for medical devices.

In an email announcing the guidance, the FDA noted that determinations of uncertainty of benefits and risks have been a part of its product reviews; however, the new guidance—titled Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemption—"makes these considerations more transparent, consistent, and objectively defined."

In the guidance document, the FDA wrote that it believes the approach described "promotes the public health by helping patients have timely access to new medical devices meeting the applicable statutory standard for safety and effectiveness, such that probable benefits of device use outweigh the probable risks and the device will provide clinically significant results in a significant portion of the target population, based on the totality of the valid scientific evidence."

In addition to considering the extent of probable benefits and risks for a given device, the FDA said that it looks at the "appropriateness of risk mitigations and the collection of postmarket data to address the uncertainty in the benefit-risk information."

Several other factors are relevant to the agency's determination of benefits and risk related to devices, including:

  • The perspectives of patients regarding uncertainty about the probable benefits and risks of a device (if available).
  • The degree of need related to public health (e.g., benefit-risk profile of other available treatments, seriousness of the health condition, portion of the patient population for whom a positive benefit-risk profile exists).
  • How much clinical evidence can be generated premarket based on appropriate considerations (e.g., the prevalence of a health condition).
  • Whether remaining uncertainty related to a device’s benefit-risk profile can be reduced or resolved postmarket.
  • The likely impact of mitigation strategies, such as labeling and other tools, that might contribute to a reasonable assurance of safety and effectiveness.
  • The nature of the decision being made (e.g., more uncertainty is likely to exist for a device’s benefit-risk profile based on the evidence submitted in an HDE application compared with a PMA, as a result of the standards for approval being different).
  • The degree of probable benefit resulting from patients having earlier access to a device.

The FDA also wrote in the guidance that its "decisions operate in the context of a broader healthcare system, where there is inherent uncertainty in the provision of healthcare, including uncertainty about how the general benefit-risk profile of a given medical product or procedure will translate to an individual patient’s health outcome, differences in regional and local medical practice, and continually evolving standard of care."

For stakeholders who are interested in learning more about the final guidance, the FDA will be hosting a webinar on October 16.